{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:39:57Z","timestamp":1791509997554,"version":"4.3.4"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":48,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Citryll BV"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neutrophil extracellular traps (NETs) are web-like structures composed of DNA, histones, and granule proteins released by activated neutrophils. While originally characterized as part of the innate immune response, NETs are now recognized as contributors to the pathogenesis of immune-mediated inflammatory diseases, including rheumatoid arthritis (RA). This review summarizes current clinical evidence linking NETs to RA, with a focus on their utility as biomarkers for disease activity and treatment response and their potential mechanistic role in disease progression. Elevated levels of NET components, such as myeloperoxidase\u2013DNA complexes, citrullinated histones, and calprotectin, have been reported in RA and correlate with inflammatory markers and clinical disease activity scores. Treatment with biological disease-modifying anti-rheumatic drugs, including tumour necrosis factor alpha and interleukin-6 inhibitors, reduces NET markers, whereas persistent NET formation is associated with poor response. NETs also promote pathogenic processes, including anti-citrullinated protein antibody formation, Th17 activation, and osteoclastogenesis. Although no therapies currently target NET formation directly, preclinical studies using PAD4 inhibitors and antibodies against citrullinated histones show promising effects. Standardizing NET biomarkers and conducting longitudinal studies will be essential for clinical translation. Overall, NETs represent both a biomarker and a mechanistic driver in RA, offering a novel opportunity for therapeutic intervention.<\/jats:p>","DOI":"10.1093\/cei\/uxag011","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T12:20:53Z","timestamp":1771244453000},"source":"Crossref","is-referenced-by-count":7,"title":["Neutrophil extracellular traps in rheumatoid arthritis: biomarkers, drivers, and emerging therapeutic targets"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2131-102X","authenticated-orcid":false,"given":"Sangeeta","family":"Kumari","sequence":"first","affiliation":[{"name":"Research and Development, Citryll BV , Pivot Park, Oss ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Pardali","sequence":"additional","affiliation":[{"name":"Research and Development, Citryll BV , Pivot Park, Oss ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Meldrum","sequence":"additional","affiliation":[{"name":"Research and Development, Citryll BV , Pivot Park, Oss ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lood","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Washington , Seattle, WA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Kraan","sequence":"additional","affiliation":[{"name":"Research and Development, Citryll BV , Pivot Park, Oss ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"2026041706065061500_uxag011-B1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nrrheum.2014.80","article-title":"The multifactorial role of neutrophils in rheumatoid arthritis","volume":"10","author":"Wright","year":"2014","journal-title":"Nat Rev Rheumatol"},{"key":"2026041706065061500_uxag011-B2","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1093\/rheumatology\/keq045","article-title":"Neutrophil function in inflammation and inflammatory diseases","volume":"49","author":"Wright","year":"2010","journal-title":"Rheumatology"},{"key":"2026041706065061500_uxag011-B3","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"2026041706065061500_uxag011-B4","doi-asserted-by":"crossref","first-page":"662","DOI":"10.3389\/fimmu.2020.00662","article-title":"Identification of specific joint-inflammatogenic cell-free DNA molecules from synovial fluids of patients with rheumatoid arthritis","volume":"11","author":"Dong","year":"2020","journal-title":"Front Immunol"},{"key":"2026041706065061500_uxag011-B5","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/art.41062","article-title":"A neutrophil activation biomarker panel in prognosis and monitoring of patients with rheumatoid arthritis","volume":"72","author":"Bach","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"2026041706065061500_uxag011-B6","doi-asserted-by":"crossref","first-page":"178ra40","DOI":"10.1126\/scitranslmed.3005580","article-title":"NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis","volume":"5","author":"Khandpur","year":"2013","journal-title":"Sci Transl Med"},{"key":"2026041706065061500_uxag011-B7","doi-asserted-by":"crossref","first-page":"R122","DOI":"10.1186\/ar4579","article-title":"Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility","volume":"16","author":"Chowdhury","year":"2014","journal-title":"Arthritis Res Ther"},{"key":"2026041706065061500_uxag011-B8","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3389\/fimmu.2019.00423","article-title":"Caught in a trap? 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